Inflammatory disease, in the modern era, is one of the important disease fields for which countermeasures are necessary. Steroids, aspirin and ibuprofen, which are called nonsteroidal anti-inflammatories (NSAIDs), and other such substances are representative of drugs currently used as anti-inflammatories.
Among these substances, steroids are used in the treatment of both acute and chronic inflammatory conditions in the clinical setting due to their potent effect. However, problems such as acquisition of resistance due to frequent use, adverse effects, and the like have been pointed out.
Since NSAIDs have an antipyretic analgesic action, they are used as symptomatic therapy. However, it is also known that in NSAIDs, when taken for an extended period of time, damage the gastrointestinal tract, increase the risk of cardiac disease, and allow the progression of inflammatory tissue damage, and this has become a serious problem (Non-patent References 1 and 2).
Substances having hydroxyl groups at position 18 and position 5 of eicosapentaenoic acid (EPA) called resolvin E1 (RvE1: 5S,12R,18R-trihydroxyeicosapentaenoic acid) and other such resolvins and derivatives thereof and substances having hydroxyl groups at position 10 and position 17 of docosahexaenoic acid (DHA) called protectin D1 (PD1) and derivatives thereof are also known to have anti-inflammatory activity (Non-patent References 3 and 4).
The applicant discovered and applied for a patent (International Application PCT/JP2010/52509) on compounds relating to specific dihydroxy forms of eicosapentaenoic acid and docosahexaenoic acid which differ from resolvins and protectins (8,18-dihydroxyeicosapentaenoic acid (8,18-diHEPE), 11,18-dihydroxyeicosapentaenoic acid (11,18-diHEPE), 12,18-dihydroxyeicosapentaenoic acid (12,18-diHEPE), 17,18-dihydroxyeicosapentaenoic acid (17,18-diHEPE). 10,20-dihydroxydocosahexaenoic acid (10,20-diHDoHE), 13,20-dihydroxydocosahexaenoic acid (13,20-diHDoHE), 14,20-dihydroxydocosahexaenoic (14,20-diHDoHE), 19,20-dihydroxydocosahexaenoic (19,20-diHDoHE), and the like).
Derivatives of eicosapentaenoic acid and docosahexaenoic acid which differ from resolvins and protectins are reported to some extent in Patent Reference 1 in addition to the above application. However, there is no mention or suggestion whatsoever of epoxide compounds of eicosapentaenoic acid and docosahexaenoic acid and the like, especially ω3 epoxy compounds further made into hydroxy compounds. Moreover, there is no proof whatsoever that such compounds actually possess anti-inflammatory activity. Non-patent Reference 5 mentions a methyl ester of 4hy-19,20-EpDPE.